High-affinity kainate receptor subunits are necessary for ionotropic but not metabotropic signaling

Neuron. 2009 Sep 24;63(6):818-29. doi: 10.1016/j.neuron.2009.08.010.


Kainate receptors signal through both ionotropic and metabotropic pathways. The high-affinity subunits, GluK4 and GluK5, are unique among the five receptor subunits, as they do not form homomeric receptors but modify the properties of heteromeric assemblies. Disruption of the Grik4 gene locus resulted in a significant reduction in synaptic kainate receptor currents. Moreover, ablation of GluK4 and GluK5 caused complete loss of synaptic ionotropic kainate receptor function. The principal subunits were distributed away from postsynaptic densities and presynaptic active zones. There was also a profound alteration in the activation properties of the remaining kainate receptors. Despite this, kainate receptor-mediated inhibition of the slow afterhyperpolarization current (I(sAHP)), which is dependent on metabotropic pathways, was intact in GluK4/GluK5 knockout mice. These results uncover a previously unknown obligatory role for the high-affinity subunits for ionotropic kainate receptor function and further demonstrate that kainate receptor participation in metabotropic signaling pathways does not require their classic role as ion channels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Biotinylation / methods
  • Electric Stimulation / methods
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / cytology
  • In Vitro Techniques
  • Mice
  • Mice, Knockout
  • Microscopy, Immunoelectron / methods
  • Neurons / cytology
  • Neurons / physiology
  • Patch-Clamp Techniques / methods
  • Presynaptic Terminals / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / physiology*
  • Receptors, Kainic Acid / classification
  • Receptors, Kainic Acid / deficiency
  • Receptors, Kainic Acid / physiology*
  • Signal Transduction / physiology*
  • Synapses / metabolism
  • Synapses / physiology
  • Synapses / ultrastructure


  • Protein Subunits
  • Receptors, Kainic Acid